The objective of this proposal is to develop aromatase (estrogen synthetase) inhibitors for clinical application in the areas of male and female contraception, endometriosis and premature labor. In order to determine how the compounds would be most effective as long-acting contraceptive agents in the female, studies would be conducted to investigate the role of estrogen in follicular recruitment and maturation in the rat ovary. Studies would be extended to the primate to determine the most effective schedule of treatment to inhibit estrogen production and ovulation. Aromatase inhibitor 4-hydroxyandrostene-3, 17-dione (4-OHA) would be evaluated in experimental endometriosis by studying the effect of 4-OHA on growth of endometrial explants sutured to the body wall of the rat. 4-OHA would also be evaluated in male rats for its effect on testicular aromatase, plasma testosterone concentrations and spermatogenesis. Hyperprolactinemia is a major cuase of infertility in women and during lactation prolactin levels are high. During the current grant period, inhibition of aromatase by prolactin was demonstrated in vivo in the rat. Studies are proposed to investigate the mechanism of prolactin inhibition of aromatase. In vitro cultures of rat ovarian granulosa cells will be used to study prolactin-mediated changes in gonadotropin and prolactin receptors, cAMP concentration and aromatase activity.